von Willebrand disease

Kaipol Takpradit

● Introduction to von Willebrand factor● von Willebrand disease● Type of von Willebrand disease● Management of von Willebrand disease

Topic

● Named after Dr. Erik von Willebrand who describe hereditary bleeding disorder distinguished from hemophilia in 1924

● The protein was purified in 1970s● Produced in megakaryocyte, endothelium,

subendothelial CNT● Size 250 kDa for monomer and up to

more than 20,000 kDa for multimer

von Willebrand factor

● Has functions of binding for platelet, FVIII, and collagen

● Bind platelet to exposed collagen● Chaperone of FVIII● Cleaved by ADAMTS-13 protein at A2

domain and eliminated by liver and spleen

von Willebrand factor

von Willebrand factorFVIII chaperone

Platelet GPIb binding

ADAMTS-13 cleavage site

Collagen binding GPIIbIIIa binding

von Willebrand disease

● Manifestation of platelet binding problem or severely decrease FVIII half life

● Present with mucocutaneous bleeding● Or hemophilia-like in type 2N and type 3● History of bleeding diathesis in first-degree

relatives● Significant bleeding may be determined by

bleeding score of 3 in male and 5 in female

Bleeding score

Bowman M, et al. J Thromb Haemost. 2008:6(12);2062-66.

●Type 1: vary degree of decrease, vWF:Rco/vWF:Ag > 0.6●Type 1 Vicenza: normal production and secretion of vWF but has increase excretion●A person with blood group O has lower vWF level than other ABO blood group

Type of von Willebrand disease

●Type 2: abnormal function○ 2A: decreased larger multimer, vWF:

Rco/vWF:Ag < 0.6○ 2B: increase affinity to platelet, hyper-

response to RIPA○ 2M: decrease affinity to platelet GPIb○ 2N: decrease affinity to FVIII, FVIII:

c/vWF:Ag< 0.5●Type 3: severe or totally absence of vWF

Type of von Willebrand disease

●The goal is to prevent bleeding●Identify patients with increased bleeding risk●Patients with vWF level > 40 UI/dL or without history of bleeding are not at risk of bleeding●Desmopressin is the first line of treatment

Management of vWD

Management of vWD

●Desmopressin infusion trial can determine response of the patient●If vWF:Rco/Ag near normal and level > 30 UI/dL with low bleeding risk usually response to desmopressin●For patients with type 2b or type 3 and patients who do not respond to desmopressin factor replacement is required

●Increase vWF secretion from endothelial Weibel-Palade bodies or from platelet α-granule●Dose 0.3 mcg/kg IV or SC●150-300 mcg intranasal●Check for level at 1 and 4 hr to access the response●Repeat at 12-24 hr up to 3-4 doses●Tachyphylaxis after continuous dose●Fluid pretension must be aware off

Desmopressin infusion trial

Replacement therapy

● vWF hemostat level 20-50%,half life 20-40 hr

● Use FVIII conc. that contain vWF 40-60 U/kg then 40-50 U/kg q 12-24 hr up to 7 days

● Cryoprecipitate 1 U/ 10 kg OD

Antifibrinolytic

● Tranexamic acid may help in case of minor bleeding for hypermenorrhea

● Dose 25 MKDose for oral and 10 MKDose for IV 3-4 times/day

● Renal impairment require dose reduction● Should be avoid in patient with high

cardiovascular risk

For pregnancy

● vWF usually increase in near-term period● Serial checking in the last trimester is

recommended● Desmopressin can be administered right

after an umbilical cord is cut● Replacement immediately (40-50 U/kg)

before delivery and at 24 and 72 hr later (20-30 U/kg)

● Antifibrinolytic can relieve excessive lochia

Inheritance

● Autosomal Dominant● Except type 2n, 3 -> autosomal recessive

Question?

FIN